In order to gain further information on the role of adrenergic neurotransmitters in the functions and dysfunctions of the nervous system we plan to continue the present studies with some changes in emphasis in certain areas. A part of our study will be devoted to isolation and characterization of catecholamine synthesizing enzymes. With immunohistochemical techniques we will study the functions of the neurotransmitters on the cellular level. It is also planned to carry out similar studies at the ultrastructural levels. Using recently developed procedures, we will analyze DBetaH in human serum and CSF in various physiological and pathological states. In these studies we will determine whether some pathophysiology of brain disease is associated with aberrations of the adrenergic system. We will also investigate whether the biochemical abnormalities in patiets with psychiatric disorders show a familial trend. Genetic variations in catecholamine synthesizing enzymes will be studied in multiple inbred mouse strains. The mechanisms involved in the regulation of catecholamine synthesis will be investigated in various experimental models. The role of cyclic nucleotides and of the neuroendocrine system in the regulation of catecholamine synthesis will be investigated. Attempts will be made to isolate and to characterize adrenergic receptors and to study the properties of these functional proteins on the molecular level.